The differential diagnosis of chorea

Chorea is a hyperkinetic movement disorder characterised by excessive spontaneous movements that are irregularly timed, randomly distributed and abrupt. In this article, the authors discuss the causes of chorea, particularly Huntington's disease and the genetic syndromes that may resemble it, including HDL1-3, inherited prion disease, spinocerebellar ataxias 1, 3 and 17, neuroacanthocytosis, dentatorubro-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia and mitochondrial disease. Acquired causes of chorea include vascular disease, post-infective autoimmune central nervous system disorders (PANDAS), drugs, systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, AIDS, chorea gravidarum, and polycythaemia rubra vera. The authors suggest an approach to the clinical assessment of chorea, the value of investigations, including genetic tests (for which they offer a structured framework highlighting the importance of prior counselling), and finally briefly discuss symptomatic drug treatment of chorea

The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician

A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features (‘red flags’) that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive–behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years

Late onset of Huntington's disease

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease

Anti-CV2/CRMP5 Paraneoplastic Chorea Effectively Managed with Intravenous Amantadine

Background: Paraneoplastic chorea is typically a subacute progressive hyperkinetic movement disorder. The mainstay of treatment is managing the underlying neoplasm. However, the clinical course may be variable, and effective symptomatic management can precede the start of cancer treatment. Case report: A 63-year-old man presented with insidious onset, slowly progressive generalized chorea for 1 year, later diagnosed as anti-CV2/CRMP5 autoantibody positive paraneoplastic chorea. His chorea was markedly improved with intravenous amantadine. Discussion: In patients with anti-CV2/CRMP5 autoantibody-related chorea, sequential follow-up of brain magnetic resonance imaging reveals progression from active inflammation to atrophy. Our report highlights the efficacy of intravenous amantadine in paraneoplastic chorea

Anticonvulsants-induced chorea: a role for pharmacodynamic drug interaction?

AbstractChorea is a rare side effect of anticonvulsants. We describe three patients who developed chorea secondary to anticonvulsant combination use. A mechanism to explain this finding is proposed.After identification of an index case with anticonvulsant-induced chorea, we reviewed the electronic data base records for all patients with seizures followed in the epilepsy clinics at our university-based hospital for cases of dyskinesia associated with anticonvulsants. Two additional patients , one adult and one pediatric patient were identified.Three patients developed chorea while receiving combination anticonvulsants. Two patients had transient chorea that resolved with withdrawal of one of the drugs. All three patients were using phenytoin and lamotrigine in combination when the chorea started, chorea improved with tapering one of the medications.Polytherapy with certain anticonvulsants may predispose patients to drug-induced chorea. A particular increased risk was seen with combinations that have phenytoin and lamotrigine. This could be due to an additive or a synergistic effect on central dopaminergic pathways

Therapeutic decision making in autoimmune and inflammatory disorders of the central nervous system in children.

ABSTRACT Autoimmune and inflammatory disorders of the central nervous system can result in significant morbidity and mortality. Through the recognition of syndromes using diagnostic biomarkers, the clinician is now able to use immune suppressive therapies to improve outcomes. However, the therapeutic decision-making process is complex. The clinician has to balance the risk of disease, with the risk of treatment side effects. To achieve this balance, it is important to understand the natural history of disease, the risk of residual disability, the risk of relapse, and risk of a fatal outcome. It is also important to have some understanding of the pathological processes, as some of the entities have more reversible processes, whereas others have destructive processes. This review will assess the dynamic nature of this decision-making process, and compare some of the more severe diseases such as neuromyelitis optica, anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus myoclonus ataxia syndrome, with disorders with more favourable outcomes such as Sydenham chorea and post-infectious cerebellar ataxia

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Therapeutic decision making in autoimmune and inflammatory disorders of the central nervous system in children.

ABSTRACT Autoimmune and inflammatory disorders of the central nervous system can result in significant morbidity and mortality. Through the recognition of syndromes using diagnostic biomarkers, the clinician is now able to use immune suppressive therapies to improve outcomes. However, the therapeutic decision-making process is complex. The clinician has to balance the risk of disease, with the risk of treatment side effects. To achieve this balance, it is important to understand the natural history of disease, the risk of residual disability, the risk of relapse, and risk of a fatal outcome. It is also important to have some understanding of the pathological processes, as some of the entities have more reversible processes, whereas others have destructive processes. This review will assess the dynamic nature of this decision-making process, and compare some of the more severe diseases such as neuromyelitis optica, anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus myoclonus ataxia syndrome, with disorders with more favourable outcomes such as Sydenham chorea and post-infectious cerebellar ataxia

Progression of motor subtypes in Huntington’s disease. a 6-year follow-up study

The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington's disease (HD) and their relationship with cognitive and general functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (n = 891), hypokinetic-rigid (n = 916), or mixed-motor (n = 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles